Dissecting Dyshomeostasis in Neural Aging and Disease: Insights from Spatial Omics and Molecular Imaging

Dysregulation of lipids, metabolites, and proteins is increasingly recognized as a key driver of brain aging and of the onset and progression of neurological diseases, including neurodegenerative and neuropsychiatric disorders. Historically, our understanding of lipid and small-molecule metabolism - and of protein alterations - has relied largely on measuring enzyme expression/activity and bulk protein abundance. While informative, these approaches often miss the spatiotemporal dynamics of molecular changes across the brain.This gap matters: aging and disease progression are shaped by brain-region specificity and cell-type selective vulnerability, with disruptions emerging early in particular anatomical and cellular niches. Recent advances in spatially resolved omics and molecular imaging - including imaging mass spectrometry and complementary computational approaches—now enable high-resolution mapping of lipids, metabolites, and proteins at regional and, increasingly, cellular scales. Combined with system-level lipidomics, metabolomics, and proteomics datasets, these technologies are helping to pinpoint the anatomical sites and cell populations that show early and persistent dyshomeostasis, ultimately contributing to clinical phenotypes.This Research Topic will highlight cutting-edge work that integrates omics profiling with spatial methodologies to preserve anatomical context and improve mechanistic insight. Contributions are encouraged that (i) identify molecular alterations linked to pathology and disease stage, (ii) test hypotheses about disrupted metabolic and signaling networks in neural aging and neurodegeneration, and (iii) develop robust molecular signatures and biomarkers for earlier detection, stratification, and therapeutic monitoring.Innovative molecular imaging and spatial omics methods, including imaging mass We welcome articles addressing, but not limited to, the following themes: • Innovative molecular imaging and spatial omics methods, including imaging mass spectrometry, multiplexed approaches, and computational pipelines for mapping lipids, metabolites, and proteins in neural tissue • System-level lipidomic, metabolomic, and proteomic profiling and its implications for brain function and dysfunction • Mechanisms of dyshomeostasis in neural aging and in neurodegenerative/neuropsychiatric conditions • Spatial and longitudinal molecular signatures of neural aging (region- and cell-type resolved when possible) • Biomarker development (lipid, metabolic, and/or protein) for early detection, progression tracking, and patient stratificationTopic Editor Prof. Sommella is the founder of ARACNE BIONTECH S.r.l. and SONDA S.r.l.; these activities are independent of this Research Topic and do not affect his editorial role. Topic editors: Laura Beth McIntire, Merina Varghese, Eduardo Sommella Source: https://www.frontiersin.org/research-topics/72559/dissecting-dyshomeostasis-in-neural-aging-and-disease-insights-from-spatial-omics-and-molecular-imaging